The long-term goal of this study is to understand the mechanisms governing morphogenesis of the GI tract and the underlying causes of GI malformations. In the current view, the neural crest cells are the sole neural tube-derived cells contributing to the development of the GI tract, by forming the enteric nervous system (ENS). However, our preliminary results indicate that a heretofore unrecognized population of neural tube- derived cells also contributes to the development of the ENS and non-neural cells in the foregut. These cells, termed as the Ventrally Emigrating Neural Tube (VENT) cells, originate from the ventral part of the hindbrain, and colonize the foregut in association with the vagus nerve. Several different observations have prompted us to hypothesize that the VENT cells make specific contributions to the morphogenesis of the GI tract. The hypothesis will be tested in avian embryos by determining the specific fate and capabilities of the VENT cells by using microsurgical tissue transplantation, chorioallantoic membrane grafting, immunocytochemistry, in situ hybridization, and electron microscopy. The specific aims are to: (1) Determine the specific derivatives and relative contributions of the VENT cells to the ENS of the foregut. (2) Determine the non-neural derivatives of the VENT cells in the foregut. (3) Determine if the VENT cells are pre-specified to the neural or non-neural fate in the foregut. (4) Determine whether the VENT cells can colonize the midgut and form the ENS. (5) Determine whether the VENT cells can give rise to the ENS in the hindgut. (6) Determine whether the VENT cells from an inappropriate region are capable of forming the ENS. Results of this study should provide significant new information by indicating the specific contributions and capabilities of an additional neural tube-derived cell population to the development of the GI tract, which may lead to a revision of one our current concepts, that the neural crest cells are the sole neural tube-derived cells contributing to the development of the GI tract. Results may also help in understanding the cause of some of the GI malformations, such as the Hirschsprung's disease. PI::I-{I-L)I,t.MANCI-- _111.-(;5) (organization, city, state) Medical College of Georgia Augusta, Georgia KEY PI:R[SUNNL:L. :See instructions. Use continuation pages as neededtO provide the required intormat_on in tr}e tormat shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name Organization Role on Project Gurkirpal S. Sohal Medical College of Georgia PI Disclosure Permission Statement. Applicable to SBIR/STTR Only. See instructions. [] Yes [] No [unreadable] PHS 398 (Rev. 05/01) Page _2 Form Page 2 [unreadable] [unreadable] Principal Investigator/Program Director (Last, first, middle): Sohal, Gurkirpal S. The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .................................................................................................................................................. 1 Description,